title: Differential and isomer-specific modulation of vitamin A transport and the catalytic activities of the RBP receptor by retinoids.
abstract: Retinoids are vitamin A derivatives with diverse biological functions. Both natural and artificial retinoids have been used as therapeutic reagents to treat human diseases, but not all retinoid actions are understood mechanistically. Plasma retinol binding protein (RBP) is the principal and specific carrier of vitamin A in the blood. STRA6 is the membrane receptor for RBP that mediates cellular vitamin A uptake. The effects of retinoids or related compounds on the receptor's vitamin A uptake activity and its catalytic activities are not well understood. In this study, we dissected the membrane receptor-mediated vitamin A uptake mechanism using various retinoids. We show that a subset of retinoids strongly stimulates STRA6-mediated vitamin A release from holo-RBP. STRA6 also catalyzes the exchange of retinol in RBP with certain retinoids. The effect of retinoids on STRA6 is highly isomer-specific. This study provides unique insights into the RBP receptor's mechanism and reveals that the vitamin A transport machinery can be a target of retinoid-based drugs.
authors.affiliation: Department of Physiology, Jules Stein Eye Institute, and Howard Hughes Medical Institute, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
authors.forename: Riki
authors.initials: R
authors.lastname: Kawaguchi
authors.affiliation: Department of Physiology, Jules Stein Eye Institute, and Howard Hughes Medical Institute, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhong
authors.affiliation: Department of Physiology, Jules Stein Eye Institute, and Howard Hughes Medical Institute, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
authors.forename: Miki
authors.initials: M
authors.lastname: Kassai
authors.affiliation: Department of Physiology, Jules Stein Eye Institute, and Howard Hughes Medical Institute, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
authors.forename: Mariam
authors.initials: M
authors.lastname: Ter-Stepanian
authors.affiliation: Department of Physiology, Jules Stein Eye Institute, and Howard Hughes Medical Institute, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Sun
mesh_terms: D000818:Animals; D001692:Biological Transport; D002384:Catalysis; D002460:Cell Line; D006801:Humans; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012176:Retinoids; D014801:Vitamin A / Q000378:metabolism*
chemical_list: D011956:Receptors, Cell Surface; D012176:Retinoids; C027928:retinol binding protein receptor; D014801:Vitamin A